Recovering from cocaine: Insights from clinical and preclinical investigations

Abstract

Cocaine remains one of the most addictive substances of abuse and one of the most difficult to treat. Although increasingly sophisticated experimental and technologic advancements in the last several decades have yielded a large body of clinical and preclinical knowledge on the direct effects of cocaine on the brain, we still have a relatively incomplete understanding of the neurobiological processes that occur when drug use is discontinued. The goal of this manuscript is to review both clinical and preclinical data related to abstinence from cocaine and discuss the complementary conclusions that emerge from these different levels of inquiry. This commentary will address observed alterations in neural function, neural structure, and neurotransmitter system regulation that are present in both animal models of cocaine abstinence and data from recovering clinical populations. Although these different levels of inquiry are often challenging to integrate, emerging data discussed in this commentary suggest that from a structural and functional perspective, the preservation of cortical function that is perhaps the most important biomarker associated with extended abstinence from cocaine.

Neurofunctional Reward Processing Changes in Cocaine Dependence During Recovery

“…Gaining a better idea of neurofunctional changes during treatment represents an important first step in understanding the neurobiology of successful abstinence (Garavan et al, 2013;Hanlon et al, 2013). Additionally, our findings of increased precuneus/PCC activity during A2Win are consistent with a recent meta-analysis citing common effects of pharmacological and cognitive-based interventions in these areas (Konova et al, 2013).…”

“…Although many neuroimaging studies examine chronic effects of cocaine on cognitive processes, relatively few examine brain changes occurring with discontinued drug use (Garavan et al, 2013;Hanlon et al, 2013). Investigating neurofunctional changes associated with abstinence may provide important insights regarding strategies for cessation and relapse prevention (Garavan et al, 2013;Hanlon et al, 2013).…”

Serotonin 5-HT2Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

“…Compared with control subjects, cocaine users have lower resting-state functional connectivity within the mesolimbic DA system and lower network connectivity between limbic regions is correlated with duration of cocaine use (Gu et al, 2010). Indeed, a recent review article concluded that loss of PFC function during abstinence could be the most reliable clinical biomarker of relapse (Hanlon et al, 2013;Bough et al, 2014).…”

Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector-Delivered Cocaine Hydrolase

“…This leads to a prolonged cycle of abuse, treatment, and relapse (e.g., Griffin et al, 1989;Vonmoos et al, 2013). Neurologic decrements from long-term cocaine intake may persist a year beyond cessation of use (review by Hanlon et al, 2013). These can include impaired attention, working memory, and executive function (Vonmoos et al, 2013(Vonmoos et al, , 2014, possibly owing to decreased frontal lobe activity (Volkow et al, 1992;Connolly et al, 2012).…”